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Non Small Cell Lung CancerPhase 1PARISNCT03245177

Pembrolizumab in Combination With Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

A Phase 1 study testing Pembrolizumab and Radiotherapy in people with Non Small Cell Lung Cancer, run by Prof Corinne Faivre-Finn.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Lung cancer is the leading cause of cancer mortality worldwide and in the U.K alone; there are 38,000 new cases of non-small cell lung cancer (NSCLC) a year. The new treatment being tested in this study is called pembrolizumab, this is a type of immunotherapy, which works by stimulating the body's own immune system to… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
Pembrolizumab and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Aug 2017to 1 Aug 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed NSCLC
  • Unresectable stage III NSCLC not suitable for concurrent chemoradiotherapy i.e;
  • Patient unsuitable for cisplatin (eg poor renal function);
  • Large volume of disease with predicted dose to thoracic organs at risk that are likely to exceed the constraints for concurrent chemoradiotherapy, in the opinion of a clinical oncologist specialised in lung cancer
  • Stage IV NSCLC with dominant chest symptoms and low burden of metastatic disease who may benefit from thoracic RT
  • Patient considered suitable for radical radiotherapy
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  • If chemotherapy has been given previously, the maximum interval between the last day of chemotherapy and the start of radiotherapy must be 6 weeks. The minimum interval between the last day of chemotherapy and the start of Pembrolizumab must be one week
  • Age ≥ 18
  • Life expectancy estimated to be greater than 6 months
  • Performance status (ECOG) 0 or 1 (see Appendix 1)
  • MRC dyspnoea score < 3 (see Appendix 2)
  • FEV1 ≥ 40% predicted and DLCO ≥ 40% predicted; Lung V20 ≤ 30% in the dose finding part of the study and ≤ 35% in the expanded cohort
  • No prior thoracic radiotherapy (excluding patients that have had RT for Breast cancer providing that the overlap is minimal as per local investigators discretion or as discussed and agreed by CI as required) or T cell modulating antibodies (including anti-PD-1, anti-PD-L1, PD-L2, anti-CD137 and anti-CTLA4, including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Measurable disease based on RECIST 1.1
  • Patient willing to undergo a repeat biopsy post RT
  • Written informed consent must be given according to GCP and national regulations.
  • Adequate organ function within 7 days of study treatment as defined in the protocol.

Who cannot join

  • Mixed non-small cell and small cell tumours
  • Participation in a study of an investigational agent or using an investigational device within 4 weeks prior to the anticipated start of treatment.
  • Current or previous malignant disease within 3 years except CIN, non-melanoma skin cancer and low grade, low stage prostate cancer found as incidental finding and not requiring treatment
  • History of interstitial pneumonitis (to include diffuse alveolar damage, non-malignant causes of pneumonitis, acute respiratory distress syndrome, alveolitis, cryptogenic organising pneumonia, obliterative bronchiolitis, non-malignant causes of pulmonary fibrosis)
  • Presence of brain metastases confirmed by CT or MR brain (unless suitable for local treatment such as SRS or Neurosurgery)
  • History of autoimmune disease requiring steroids or immunosuppressive medication
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  • Uncontrolled hypothyroidism or hyperthyroidism
  • Other diseases requiring immunosuppressive therapy greater than 28 days prior to the anticipated first dose of trial treatment.
  • Other diseases requiring systemic glucocorticoid (doses <=10 mg prednisolone or equivalent) prior to the first dose of trial treatment.
  • Received a prior autologous or allogeneic organ or tissue transplantation.
  • Chronic GI disease likely to interfere with protocol treatment.
  • Testing positive for human immunodeficiency virus, active hepatitis B or C infection.
  • Treatment with live vaccine within 30 days prior to the first dose of trial treatment.
  • Patients of reproductive potential who are unable to comply with effective contraception if sexually active during the study and for up to 120 days after the last dose of Pembrolizumab
  • Women who are pregnant or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

About this study

Official title: A Phase I Study of Pembrolizumab Anti PD-1 Monoclonal Antibody in Combination With Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer mortality worldwide and in the U.K alone; there are 38,000 new cases of non-small cell lung cancer (NSCLC) a year. The new treatment being tested in this study is called pembrolizumab, this is a type of immunotherapy, which works by stimulating the body's own immune system to fight cancer cells.

Pembrolizumab blocks a protein on the T-cell surface (one of the cells of the immune system), which then triggers the cell to find and kill cancer cells. This will be given with radiotherapy to see if this combination is safe and effective at treating patients with non-small cell lung cancer.

Pembrolizumab has proved to be a safe and effective treatment for other cancers such as melanoma and lung cancer. Radiotherapy is often given as standard treatment to treat lung cancer, and is proven to be a safe and tolerable treatment. However, the safety of the combination of Pembrolizumab and thoracic radiotherapy delivered concurrently has not been tested yet prospectively

Being tested
Pembrolizumab, Radiotherapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Anti-PD-1 antibody

  • RadiotherapyRadiation

    60-66 Gy in 30-33 fractions, 2 Gy per fraction

Study groups in NCT03245177
Study groupRoleWhat they receive
Pembrolizumab plus radiotherapyExperimentalPembrolizumab is given by intravenous infusion over 30 minutes at a maximum dose of 200mg. The first dose of pembrolizumab is administered 14 days prior to the initiation of radiotherapy and every 3 weeks thereafter. Radiotherapy is given as a standard dose (60-66 Gy in 2 Gy/fraction) over 40-45 days (daily on Mon-Fri) Following completion of radiotherapy, participants will continue to receive pembrolizumab every 3 weeks for up to 12 months of maintenance treatment.
Receives: Biological: Pembrolizumab; Radiation: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended phase II dose (RP2D)

    The dose level at which < 2/6 participants experience dose limiting toxicity (DLT).

    Measured: Within the period from the start of treatment until 12 weeks after completion of combined pembrolizumab and thoracic radiotherapy

  2. Dose limiting toxicity

    Non-haematologic:

    Any ≥grade 3 non-haematological toxicity definitely, probably or possibly related to the combination of Pembrolizumab and thoracic radiotherapy including:

    • Increased MRC dyspnoea score >2 grades from baseline or CTCAE dyspnoea grade ≥3 persisting for >7 days
    • Pneumonitis grade ≥4, or grade ≥3 persisting for >7 days despite optimal medical management.
    • Oesophagitis grade ≥4, or ≥3 persisting for >7 days despite optimal medical management
    • Toxicity leading to interruption of radiotherapy for >4 days. Any grade 4 toxicity that has not previously been reported with pembrolizumab and is considered at least possibly related to the combination of pembrolizumab with radiotherapy

    Haematologic:

    • Neutropenia ≥grade 3 with fever >38.5
    • Thrombocytopaenia ≥grade 4.

    Any other event, in the opinion of the Safety Review Committee, is considered to be clinically significant and related to trial treatment.

    Measured: Within the period from the start of treatment until 12 weeks after completion of combined pembrolizumab and thoracic radiotherapy.

Secondary outcomes (7)

  1. Safety profile, based on the occurrence of SAEs, SARs and SUSARs

    Measured: Until 90 days after participant completes study treatment. Assessed up to 17 months.

  2. Toxicity profile, based on the occurrence of adverse events, as assessed by CTCAE v4.0

    Measured: Until 30 days after participant completes study treatment. Assessed up to 15 months.

  3. Treatment compliance of Pembrolizumab combined with thoracic RT

    Measured: Until end of treatment for each participant.

  4. Best overall response to Pembrolizumab combined with thoracic RT (RECIST)

    Measured: Assessed for each participant from the start of the treatment until disease progression/recurrence. Assessed up to 15 months

  5. Best overall response to Pembrolizumab combined with thoracic RT (immune-related response

    Measured: Assessed for each participant from the start of the treatment until disease progression/recurrence. Assessed up to 15 months

  6. Progression Free survival

    Participants who have not progressed at the time of analysis will be censored at the last date they were known to be alive and progression free.

    Measured: Calculated for each participant from the date of registration to first documented evidence of disease progression or death. Assessed up to 15 months.

  7. Overall survival

    Participants who have not died at the time of analysis will be censored at the last date they were known to be alive.

    Measured: Calculated for each participant from the date of registration to death. Assessed up to 15 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2017
  2. Study startAug 2017 (estimated)
  3. Primary completion1 Aug 2019 (estimated)
  4. Study completion1 Aug 2019

Why it stopped: Funding withdrawn.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03245177
Sponsor's protocol ID
CFTSp103
Acronym
PARIS
Status last verified
Jul 2021
First submitted
13 Jul 2017
Last updated
28 Jul 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab and Radiotherapy in people with Non Small Cell Lung Cancer, run by Prof Corinne Faivre-Finn.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 28 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended phase II dose (RP2D) (time frame: Within the period from the start of treatment until 12 weeks after completion of combined pembrolizumab and thoracic radiotherapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03245177.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2021.

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